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Biomedical subjects

D D Hurd

Publications and source records attributed to D D Hurd.

At least 55 records · Page 3Linked to original sources
PubMed1987

Central nervous system involvement in acute nonlymphocytic leukemia. A prospective study of adults in remission.

To identify adults with acute nonlymphocytic leukemia at risk for the development of central nervous system involvement, we performed periodic cerebrospinal fluid examinations on patients in remission. Among 58 consecutive patients monitored during first remission, central nervous system leukemia developed in nine (16 percent). Four patients, including one who was symptomatic, had central nervous system leukemia detected simultaneously with marrow relapse. Five additional patients were asymptomatic and continue to have bone marrow remission. Following central nervous system and systemic treatment, two of these five patients have never had relapse, and three had relapse in the bone marrow five, 10, and 21 months later. Factors at diagnosis associated with the subsequent development of central nervous system leukemia were elevated leukocyte count, serum lysozyme and lactate dehydrogenase, extramedullary infiltration including splenomegaly, and monocytic (FAB M4 or M5a) morphology. In six of 17 patients (35 percent) with monocytic morphology, central nervous system leukemia developed compared with only three of 41 patients (7 percent) with other subtypes (p = 0.02). Discriminant analysis identified leukocyte count, splenomegaly, and M4 or M5a morphology as the most important risk factors and led to a mathematical formula that correctly identified 90 percent of the patients. Although the risk of central nervous system leukemia in adults with acute nonlymphocytic leukemia is too low to justify routine prophylaxis, those patients recognized to be at a greater risk should receive prophylaxis or be monitored closely with periodic lumbar punctures.

Acute Disease↗
PubMed1987

Invasive Scopulariopsis in the immunocompromised host.

Opportunistic infections with fungal organisms have been well described in patients undergoing intensive chemotherapy and bone marrow transplantation. In two patients, invasive infections with the saprophyte Scopulariopsis developed either following intensive chemotherapy or bone marrow transplant. Fungal disease persisted in both patients despite resection of the primary focus and prolonged treatment with the usual antifungal agents, and contributed to the death of one patient.

Acute Disease↗
PubMed1987

Allogeneic bone marrow transplantation for acute lymphoblastic leukemia in remission: prolonged survival associated with acute graft-versus-host disease.

Forty remission patients with high-risk acute lymphoblastic leukemia (ALL) underwent matched allogenic bone marrow transplantation (BMT) following preparation with cyclophosphamide and fractionated total body irradiation (TBI). As of March 1987, the median follow-up is more than 3 1/2 years. Thirteen patients are alive (11 relapse free) between 2 and 4 1/2 years post-BMT. Neither age, sex, remission number, prior extramedullary leukemia, nor WBC at diagnosis of ALL was statistically significant as a predictor of relapse-free survival. The development of acute graft-v-host disease (GVHD) in 17 patients was found, with time-dependent Cox regression analysis, to be associated with a significant reduction in post-BMT relapse risk (P = .04) and improved disease-free survival (P = .11). A prospective, randomized trial of maintenance chemotherapy with oral methotrexate and mercaptopurine did not demonstrate improvement in relapse risk or survival for those assigned maintenance chemotherapy (P = .7). These results suggest that allogeneic BMT can result in extended relapse-free survival for some patients with high-risk ALL. More effective preparative chemoradiotherapy and exploitation of the apparent graft-v-leukemia effect may be useful in future trials.

Acute Disease↗
PubMed1987

Allogeneic and autologous bone marrow transplantation for acute nonlymphocytic leukemia.

Current results show that 50% of young patients with ANLL who undergo allogeneic BMT experience prolonged DFS and may be cured. Encouraging results with high-dose chemo/radiotherapy and autologous BMT are likewise being reported. In addition, some studies using intensive postremission treatment without BMT have shown results comparable to many transplant series. As better ways of preventing GVHD are found, the morbidity and mortality of allogeneic BMT should be reduced and the benefits of transplantation for curing patients with ANLL should be increased. However, the applicability of allogeneic BMT will remain limited due to the availability of compatible donors whether related or unrelated. Further studies are needed in the use of postremission intensive therapy with and without autologous bone marrow support. However, results to date should engender the same degree of enthusiastic optimism that followed the early reports of improved outcome with allogeneic BMT when applied to first remission patients.

Acute Disease↗
PubMed1986

Correlations between immunological phenotype and karyotype in malignant lymphoma.

We have correlated immunological characteristics and karyotypic abnormalities from lymphomas in 118 patients. T-lymphomas differed significantly from B- and non-B-, non-T-lymphomas in having more normal metaphases, trisomy 19, and breaks at 1q21, 2q21, 3q27, 4q21, and 17q21 (P less than or equal to 0.03). Non-T-lymphomas had breaks in 18q in one-half the cases, but only one of 11 T-lymphomas had such breaks (P = 0.02). Among B-lymphomas, specific chromosome abnormalities were associated with the type of immunoglobulin heavy but not light chain expressed. A break at 14q22 or q24 was associated with surface delta mu-immunoglobulin (P = 0.02); trisomy 22 or a break in 22q and a break at 2q32 was associated with surface gamma-immunoglobulin (P less than 0.001); and trisomy 12 and a break at 2p13 was associated with cytoplasmic gamma-immunoglobulin (P less than 0.01). Among B-lymphomas, several cytogenetic abnormalities were associated (P less than or equal to 0.02) with expression of CD24 or CD9 surface antigens. Lack of CD24 was associated with breaks in 2p25, 5q, and 6q21; CD9 was associated with a break at 6q15. Associations with a specific immunological phenotype were not identified for cytogenetic abnormalities involving a band to which genes encoding immunoglobulin or the T-cell receptor have been localized. Breaks were common at 14q32, the genomic site of the immunoglobulin heavy chain loci, in B-, non-B-, non-T-, and T-lymphomas. In T-lymphomas this may be because this is the site of the AKT1 oncogene. Breaks were uncommonly found at the light chain loci or the genomic sites encoding the T-cell receptor. However, the recurring breakpoints associated with T-lymphomas were commonly found on chromosomes to which genes coding for various T-cell antigens have recently been provisionally assigned.

Adolescent↗
PubMed1985

Response of therapy-associated acute nonlymphocytic leukemia to intensive induction chemotherapy.

Among 31 consecutive patients who developed acute nonlymphocytic leukemia following treatment with chemotherapy or radiation therapy, 17 were treated with intensive chemotherapy aimed at inducing a complete remission. Seven of these 17 patients (41%) obtained a complete remission that ranged in duration from 2 to 11 (median 3) months. Two additional patients who failed to develop normal peripheral blood counts despite postinduction bone marrows that were normocellular and free of leukemia were classified as nonresponders. The median time to complete remission and median duration of leukopenia (WBC less than 1,000/mu 1) were 34 days and 23 days, respectively. Induction chemotherapy was complicated by fever in all patients, documented infection in six patients, and death secondary to sepsis in three. Survival of the 17 patients ranged from less than 1 to 39 (median 4) months. Patients achieving a complete remission had a median survival time of 10 months compared to 2 months for the nonresponders. The other 14 patients received only supportive care and had a median survival of 2 months. These findings indicate that therapy-associated acute nonlymphocytic leukemia (t-ANLL) can frequently respond to chemotherapy and that achieving a complete remission is associated with longer survival. Although these results are encouraging, patients with t-ANLL still have a relatively poor prognosis and efforts directed at improving treatment outcome need to be continued.

Adult↗
PubMed1985

Glucocorticoid receptors in chronic lymphocytic leukemia.

Glucocorticoid receptor (GR) levels have not been extensively studied in untreated patients with chronic lymphocytic leukemia (CLL). We have measured tumor GR levels using a whole cell assay in 18 untreated patients with CLL and correlated these levels with various in-vitro and in-vivo data. In 12 of these patients, tumor cells from more than one tissue were simultaneously studied. Measurable GR levels were found in all 36 specimens studied with median total GR levels in blood, bone marrow, and lymph nodes being 3018 (n = 17), 3524 (n = 12) and 3102 (n = 7) sites/cell respectively. GR levels did not correlate with in-vitro sensitivity, as measured by inhibition by dexamethasone of radiolabelled leucine, uridine, and thymidine uptake, nor with the clinical or laboratory features examined. Nine patients were treated with dexamethasone as a single agent; blood GR levels were not predictive of antitumor response. We conclude that in patients with CLL, malignant cells from all involved tissues have measurable numbers of GRs, but these are not correlated with in-vitro sensitivity to glucocorticoid. Blood GR levels do not correlate with antitumor response; further studies are required to see if bone marrow or lymph node receptor levels correlate with antitumor response to steroids.

Dexamethasone↗
PubMed1985

Extramedullary presentation of the blast crisis of chronic myelogenous leukaemia.

We report the clinical histories and a multiparameter pathological study of the extramedullary lesions of seven patients with chronic myelogenous leukaemia in whom the initial clinical presentation of blast crisis (BC) was in an extramedullary site (lymph nodes in six, mandibular mass in one). Bone marrow BC was demonstrated simultaneously or within a few months in four patients. Three patients received chemotherapy only, four underwent bone marrow transplant. Six patients died within 1 year from diagnosis of extramedullary BC, one is alive without disease. The longest survivals (12+, 12, 11 months) were those of patients who never developed bone marrow BC and were recipients of bone marrow transplant. Studies of extramedullary disease included: histology; histochemistry for chloracetate esterase (CAE) and lysozyme; assays for TdT; electron microscopy; immunofluorescence for Fc-receptors, immunoglobulins and lymphoid and myeloid antigens by a panel of monoclonal antibodies; and cytogenetics. Three cases were classified as myeloid BC based on histochemistry and/or ultrastructure and immunology (OKM1+, MCS2+, IG10+); two as lymphoid BC (CAE-, lysozyme-, TdT+), one of them expressing a T-cell phenotype. Cytogenetic analysis of extramedullary lesions and simultaneous or subsequent bone marrows demonstrated identical karyotypes in three patients and significantly different karyotypes in one.

Adult↗
PubMed1985

Rosette formation in malignant lymphoma.

Lymph node biopsies in a patient with follicular lymphoma showed rosette structures as seen in neuroepithelial neoplasms. These specimens were studied by histologic, immunoperoxidase (for immunoglobulins, intermediate filaments (IF), actin and neuron-specific enolase), immunofluorescence (for immunoglobulins, and with a panel of monoclonal antibodies), and electron-microscopic examination. The rosettes were formed by neoplastic lymphocytes arranged around eosinophilic fibrillary material. Ultrastructurally, this was composed of cytoplasmic processes, projecting from the lymphocytes and containing thin and intermediate filaments. Immunohistochemically, it stained for monoclonal IgM lambda, all other antigens present on the neoplastic cells, and weakly for vimentin and actin. Based on recent information about lymphocyte surface changes, it is speculated that the rosettes might represent an aggregation of neoplastic lymphocytes activated by a microenvironmental stimulus, perhaps antigen-antibody binding at the cell membrane. The practical implication of this hitherto unreported finding is that the presence of rosettes cannot be used to rule out a lymphoma.

Aged↗
PubMed1985

There are differences in cytogenetic abnormalities among histologic subtypes of the non-Hodgkin's lymphomas.

Although many recurring chromosome abnormalities have been found in malignant lymphoma (ML) in recent years, their relationship to histology remains largely undefined. We have correlated, in the same tumor mass, chromosome findings with histology, defined by the International Working Formulation for Clinical Usage, in 120 patients. We find differences among histologies in the frequency of normal metaphases and the modal number of the predominant abnormal clone. In addition, most histologies have been significantly (P less than .01) associated with specific chromosome abnormalities. In particular, ML, follicular, predominantly small cleaved cell was associated with t(14;18)(q32;q21); ML, follicular, mixed small cleaved cell and large cell with t(14;18)(q32;q21) and trisomy 8; ML, follicular, predominantly large cell with trisomy 7 and breaks in 17q21-q25; ML, diffuse, mixed small cell and large cell with breaks in 11p; ML, diffuse, large cell with trisomy 21 and breaks in 2q and 9q; ML, large cell, immunoblastic with breaks at 6q21; and ML, small noncleaved cell with t(8;14)(q24;q32). Only the associations with t(14;18) and t(8;14) have been previously reported. The associated chromosome abnormality usually occurred in 30% to 70% of a given histology, raising the possibility that cytogenetics may add important prognostic information in lymphoma as it does in the acute leukemias.

Adolescent↗
PubMed1984

Invasive Fusarium infections in bone marrow transplant recipients.

From November 1982 to September 1983, three cases of invasive infection due to Fusarium species were documented in bone marrow transplant recipients. Fusarium was cultured from discrete skin nodules (one patient), maxillary sinus (one patient), or from the blood and surgically excised nasal septum (one patient). All three isolates were resistant to 5-fluorocytosine, whereas only one isolate was resistant to amphotericin B. Although all three patients died, two of the patients had clearing of their Fusarium infection. From this experience and from a review of the literature, it is concluded that despite the dismal prognosis for immunocompromised patients with Fusarium, beneficial therapies would include systemic amphotericin B, local surgical resection, and possibly leukocyte transfusions.

Adolescent↗
PubMed1984

Allogeneic bone marrow transplantation as treatment for accelerating chronic myelogenous leukemia.

Sixteen patients with chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (BMT) when they presented with or developed objective signs suggesting acceleration of disease. Patients have been followed for a median of 515 days (range 216-806 days). Seven patients are alive from 319 to 732 days (median 538 days). Four patients are in complete remission 501-732 days after BMT. Three patients have developed cytogenetic evidence of relapse after BMT; however, these patients are alive and not dependent on therapy and have normal activity levels at 319, 515, and 550 days following BMT. Three additional patients have developed cytogenetic and hematologic evidence of relapse after BMT, progressed to blast crisis, and died. Six patients have died of other causes. Allogeneic BMT can eradicate the abnormal clone and provide normal hematopoiesis when performed during the accelerated phase of CML; however, this approach is associated with relapse and with relatively high mortality. The long-term efficacy of this approach and the relative efficacy of transplant during acceleration rather than during the chronic phase of CML have yet to be established.

Adolescent↗
PubMed1983

The chronic leukemias. Clinical picture, diagnosis, and management.

The chronic leukemias have an annual incidence in the United States of about 12,000 cases. The most common types are chronic myelogenous leukemia (CML) and chronic lymphocytic leukemia (CLL). Less common are hairy cell leukemia (HCL) and prolymphocytic leukemia (PLL). All forms have an insidious onset and vague, non-specific presenting symptoms, eg, fatigue, malaise, night sweats, weight loss. Chemotherapy is the initial treatment for CML and CLL; splenectomy, splenic irradiation, and leukapheresis may also be helpful. Splenectomy is the preferred treatment for HCL. Until recently all chronic leukemias have been ultimately fatal, but the new approach of allogeneic bone marrow transplantation now used in some cases of CML may prove to be curative if done before the disease has progressed too far.

Chronic Disease↗
PubMed1982

Successful allogeneic bone-marrow transplantation for patients in the accelerated phase of chronic granulocytic leukaemia.

Nine patients underwent allogeneic bone-marrow transplantation as treatment for chronic granulocytic leukaemia (CGL) during the accelerated phase, a point in the course of the disease when it has progressed beyond the stable chronic phase but before the onset of blast crisis. After bone-marrow transplantation, haematological and cytogenetic studies showed ablation of all evidence of leukaemia, successful engraftment, and persistence of normal haemopoiesis in all patients. In one patient severe myelofibrosis and osteosclerosis disappeared after bone-marrow transplantation. Two patients have died of complications related to graft-versus-host disease (GvHD) but with no evidence of CGL. In one patient haematological and cytogenetic evidence of recurrent disease developed after bone-marrow transplantation, and she survives in chronic phase. Six patients are free of disability, do not require transfusions, possess normal marrow chromosomes, and have persistent clinical and haematological evidence of complete remission from CGL. Intervention with allogeneic bone-marrow transplantation during the accelerated phase of CGL can eradicate the disease and can provide normal haemopoiesis with acceptably low early morbidity and mortality. The long-term efficacy of bone-marrow transplantation as treatment for CGL, and the most effective timing of the transplantation with regard to the course of disease have yet to be determined.

Adult↗
PubMed1982

15;17 Translocation in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a relatively rare subtype of leukemia that has been reported to be associated with a specific chromosome abnormality, t(15;17). It has been suggested that this translocation may have a geographical distribution and its presence may signify a poorer prognosis. In this present series of 14 patients with APL, 9 patients (64%) had the t(15;17) and 5 did not; however, no significant differences in clinical features or outcome could be found between those who did and those who did not express the translocation. When ethnic backgrounds were explored, no differences were found. More cases of the t(15;17) were found in recent years (7 of 8 patients studied since 1978 compared to 2 of 6 before 1978). This corresponded to changes made in our cytogenetic techniques suggesting that the finding of the t(15;17) may be a function of technique, rather than a real difference in disease entities, and all patients with APL may have the t(15;17) when appropriately studied.

Adult↗
PubMed1982

Reversal of severe bone marrow fibrosis and osteosclerosis following allogeneic bone marrow transplantation for chronic granulocytic leukaemia.

Severe marrow fibrosis and osteosclerosis gradually disappeared after a 33-year-old woman received an allogeneic bone marrow transplantation (BMT) as experimental treatment for chronic granulocytic leukaemia. Serial biopsies demonstrate gradual resolution of dense reticulin fibrosis, collagen fibrosis and osteosclerosis, and restoration of normal marrow architecture after transplantation. These changes correspond with histological and cytogenetic evidence of normal marrow engraftment and sustained complete remission from chronic granulocytic leukaemia. In this case severe marrow infiltration with reticulin and collagen fibrosis as well as severe derangement of marrow architecture and obliteration of the medullary cavity by osteosclerosis was an entirely reversible process after allogeneic bone marrow transplantation, and did not prevent successful engraftment, haemopoietic and cytogenetic reconstitution and complete remission from chronic granulocytic leukaemia.

Adult↗
PubMed1982

Protein A adsorption of acute myelogenous leukemia serum induces in vitro blast lysis.

We studied cytotoxic activity of acute myelogenous leukemia (AML) sera for AML blasts before and after immunoadsorption with Staphylococcus aureus, Cowan I (SAC), which contains protein A. We found in vitro that incubation with treated AML sera reduced viability to 42.7% of control (p less than 0.01) for autologous and 21.0% of control (p less than 0.01) for allogeneic blasts. Normal peripheral blood cells were not killed by treated AML sera. Wood 46 strain of Staphylococcus aureus, which does not contain protein A, did not significantly reduce AML blast viability (94.8%, p greater than 0.4), while Sepharose-bound protein A reduced viability to 63.8% (p less than 0.01). Cytotoxicity does not appear to be complement-mediated, byt cytotoxic activity is trypsin-sensitive and is contained in the immunoglobulin fraction. This model for study of the tumoricidal action of protein A adsorption should be useful for predicting utility of plasma adsorption as a therapeutic adjunct in the future.

Cytotoxicity, Immunologic↗